Effect of thymosin alpha-1 on subpopulations of Th1, Th2, Th17, and regulatory T cells (Tregs) in vitro

Thymosin alpha 1 (Tα1) has been shown to have beneficial effects on numerous immune system parameters, but little is known about the effects of Tα1 on patients with gastric carcinoma. The objective of this study was to determine the effect of Tα1 on subpopulations of Th1, Th2, Th17, and regulatory T cells (Tregs) in vitro, and to evaluate its efficacy as an immunoregulatory factor in patients with gastric carcinoma. We compared the effect of Tα1 on the frequency of CD4+ and CD8+ T cells, especially the CD4+CD25+Foxp3+ Tregs in peripheral blood mononuclear cells (PBMCs) from gastric carcinoma patients (N = 35) and healthy donors (N = 22). We also analyzed the changes in the proliferation of PBMCs in response to treatment with Tα1, and examined the production of Th1, Th2, and Th17 cytokines by PBMCs and tumor-infiltrating lymphocytes. The treatment of PBMCs from gastric cancer patients, with Tα1 (50 µg/mL) alone increased the percentage of CD4+CD25+Foxp3+ (suppressive antitumor-specific Tregs) from 1.68 ± 0.697 to 2.19 ± 0.795 percent (P < 0.05). Our results indicate that Tα1 increases the percentage of Tregs and IL-1β, TNF-α, and IL-6 in vitro.

Construction and application of a yeast expression system for thymosin a1

We want to construct a yeast expression system for thymosin a1 (Ta1) to make the orally administered Ta1 preparation possible. The whole Ta1 DNA fragment was obtained by PCR. After being digested with restriction enzymes, it was cloned into pYES2 vector. Sequencing was performed to identify the recombinant. The sequence of Ta1 in recombinant coincided with the original one reported in Genbank. When pYES2-Ta1 plasmid was transformed into yeast, galactose instead of glucose was used to induce Ta1 expression. Western blot was performed to identify the quality of the expressed Ta1. Dried yeast containing pYEST2-Ta1 was fed to Balb/c mice whose immunities were inhibited by cyclophosphamide in advance. Synthesized Ta1 peptide was used as positive control and empty yeast was used as negative control. Compared with the negative control group, both dried yeast containing pYEST2-Ta1 and synthesized Ta1 peptide can significantly increase the CD8+ level (22.74±1.09 and 18.77±4.72 vs 7.49±2.14, p<0.01), while both of them had little effect on the CD4+ lymphocytes (61.86±6.94 and 65.91±4.78 vs 57.93±10.40, p>0.05). We concluded that a high effective yeast expression system for Ta1 was constructed successfully and the Ta1 protein expressed by this system can improve CD8+ level in immune inhibited mice.

Thymosin alpha in the treatment of chronic hepatitis B: an uncontrolled open-label trial.

BACKGROUND: Interferon treatment for chronic hepatitis B has low efficacy and is associated with serious side effects. It is therefore important to assess the role of other drugs in the treatment of this condition. AIMS: To assess the efficacy and safety of thymosin alpha in 20 patients with hepatitis B-related liver disease. METHODS: Patients with chronic hepatitis B, HBV DNA positivity, ALT more than 1.5 times the upper limit of normal and liver biopsy showing chronic hepatitis or cirrhosis were treated with thymosin alpha 1.6 mg subcutaneously twice a week for 6 months. Biochemical and serological markers were assessed pre-treatment, immediately post treatment, and 6 months and 1 year after end of treatment. RESULTS: Of 20 patients, 15 had chronic hepatitis and 5 had cirrhosis on histology; 17 were HBeAg-positive and 3 were HBeAg-negative. Eight patients were interferon non-responders and 12 were naïve patients. Four patients had end-of-treatment response and two additional patients had a delayed response within 6 months of treatment; one responder had a relapse within 1 year of treatment. Overall sustained response rate was 25% (5 of 20). No patient cleared HBsAg. Reduction in ALT levels was observed after treatment and persisted one year later. No significant side effects were observed. CONCLUSION: Thymosin alpha is a safe and effective alternative treatment modality in chronic hepatitis B.

Estudo clínico-imunológico da eficácia de timomodulina (Leucogen©) na otite média aguda recorrente e na amigdalite de repetição / Assessment of efficacy and safety of thymomodulin (Leucogen©) in the prevention of recurrent otitis media and recurrent tonsillitis

Os autores realizaram estudo em 35 crianças portadoras de otite média aguda recorrente e amigdalite de repetiçäo em um estudo duplo-cego com timomodulina e placebo. As crianças tratadas com timomodulina© receberam 4mg/kg/dia do medicamento diariamente durante três meses. Foi realizado controle bioquímico antes do tratamento e com cinco meses e nove meses após o término do tratamento. Além da avaliaçäo clínica foram realizados os seguintes exames: hemograma, TGO, TGP dosagem de IgA, IgG, IgM e IgE antes do início do tratamento e nos controles. Os resultados evidenciaram tendência à diminuiçäo do número de infecçöes e o número de ciclos de antibióticos, em relaçäo a informaçäo do último ano (pré-tratamento), principalmente no grupo tratado com timomodulina, assim como tendência ao aumento do IgA e IgG após tratamento com timomodulina, o que näo ocorreu no grupo placebo. Os exames laboratoriais, contagem de eritrócitos, de hematócrito, hemoglobina, leucócitos e transaminases (TGO e TGP) näo mostraram diferenças entre os grupos, nem alteraçöes 12 meses após o início da medicaçäo, evidenciando a ausência total de toxicidade da timomodulina. Houve apenas um efeito colateral com o uso de timomodulina (náusea e vômito) numa criança com amigdalite purulenta que tomou cefalexina concomitantemente